Blood pressure and proteinuria after cessation of a brief renin-angiotensin system blockade in young and adult Lyon hypertensive rats.

The aims of the present work were to determine whether a brief renin-angiotensin system blockade with AT1 receptor antagonist or angiotensin-converting enzyme inhibitor may provide long-lasting protection against hypertension and proteinuria in both young and adult Lyon hypertensive (LH) rats. Young pre-hypertensive Lyon hypertensive rats were orally treated with 5, 10, or 20 mg/kg/d of losartan, or with 0.4 mg/kg/d of perindopril from 3 to 12 weeks of age. Adult Lyon hypertensive rats were treated with 10 mg/kg/d of losartan, 0.4 mg/kg/d of perindopril, or a combination of both from 12 to 20 weeks of age. Telemetric blood pressure (BP) and urinary protein excretion were evaluated during and after treatment cessation. In young prehypertensive Lyon hypertensive rats, losartan fully prevented the hypertension and proteinuria; these effects were dose dependent and persisted long after treatment withdrawal. When renin-angiotensin system blockade was initiated in adult Lyon hypertensive rats with established hypertension, 10 mg/kg/d of losartan or 0.4 mg/kg/d of perindopril induced a significant regression in both blood pressure (15%-20%) and proteinuria (40%-50%) as did in young Lyon hypertensive rats; the combination treatment produced an additional effect only on blood pressure. After treatment cessation, a reduction in blood pressure persisted in all the pretreated adult Lyon hypertensive rats whereas the effect on proteinuria was less marked. In conclusion, whatever the blocker used, an early renin-angiotensin system blockade in prehypertensive Lyon hypertensive rats induces a durable prevention of hypertension and associated renal alterations. The similar renin-angiotensin system blockade in adult Lyon hypertensive rats provides a regression of hypertension and proteinuria, but the persistence of these beneficial effects is less pronounced than in young Lyon hypertensive rats, thus suggesting that the treatment with renin-angiotensin system blockers should be initiated as early as possible before the full expression of hypertension, to achieve the maximal long-lasting effects in mature stage.